We propose the development of the Pyrosequencing array for genome sequencing. Pyrosequencing has widely being used by other laboratories for de novo sequencing and has a great potential for miniaturization. The aim of this proposal is to develop an exportable inexpensive device that is able to produce sequence data of million of features on a single chip. As a multidisciplinary team at Stanford University, we have already worked toward the development of such a platform. The team proposes a plan to develop this methodology to reduce the cost below $100,000 for mammalian genome sequencing. We will discuss a step-by-step development plan to achieve this goal in three years. Briefly, the proposal covers clonal amplification, miniaturized Pyrosequencing, integrated PCR, Pyrosequencing platform, an integrated fluidic and CMOS imaging platform including a signal processing unit, automation of an inexpensive platform and methodology for short read assembly to assemble a mammalian genome.